Identification of a novel amino acid deletion mutation and a very rare single nucleotide variant in a Japanese family with type I antithrombin deficiency.

We studied a Japanese family with type I antithrombin (AT) deficiency and identified a novel in-frame deletion mutation (-ATG at nucleotide position of 2771-2773) in the AT gene, which predicted loss of a methionine (Met) at amino acid number of 103. In addition, we found a single base replacement of G to A at nucleotide position of 67 (4 base upstream to the initial codon) in the mutant allele. Since the G67A substitution in the AT gene was very rare, this family was the second case, in which the nucleotide change was transmitted. To elucidate the mechanism of AT deficiency, we transiently expressed wild type and the mutant AT (DeltaM103) in HuH-7 human hepatoma cells and performed pulse-chase studies. The experiments revealed that the mutant AT (DeltaM103) hardly secreted into the medium and underwent partial intracellular degradation. In addition, we performed luciferase reporter assay to examine the effect of G67A substitution on the AT gene expression, and found that the substitution did not reduce the luciferase activity. These results suggested that secretion defect and intracellular degradation of the variant molecule with the deletion of Met 103 were responsible for AT deficiency in this family.

Cholesterol crystal embolization (CCE) after cardiac catheterization: a case report and a review of 36 cases in the Japanese literature.

Cholesterol crystal embolization (CCE) is a complication of atherosclerosis. A 67-year-old Japanese man underwent coronary artery bypass grafting. After the surgery, he underwent coronary angiography via the right femoral artery. Twelve days later, he suddenly developed acalculous cholecystitis and was treated with antibiotics. Gradual deterioration in renal function, purplish discoloration of the distal portion of his toes, and eosinophilia were noted. We performed a skin biopsy and made a diagnosis of CCE. Cilostazol and intravenous heparin improved the symptoms and decreased the creatinine level. We retrospectively studied the clinical features of 36 cases registered with a diagnosis of CCE in the Japanese literature.

Ruptured aneurysm of the sinus of valsalva coexisting with a ventricular septal defect and single coronary artery.

A 26-year-old man had been diagnosed with a cardiac murmur from birth. In 1998, he was admitted to hospital because of slight fatigue. A grade 5/6 continuous murmur was audible near the right sternal border at the second intercostal space. Doppler echocardiography detected an abnormal flow that suggested that an aneurysm of the right coronary sinus of Valsalva had ruptured into the right ventricular inflow tract. Blood tests showed a 19% step-up in oxygen saturation value between the right atrium and right ventricle, indicating a ventricular septal defect with left to right shunt. Coronary angiography revealed a single coronary artery. Surgical repair was carried out and the patient made an uneventful recovery. This rare combination of a ruptured aneurysm of the sinus of Valsalva coexisting with a ventricular septal defect and a single coronary artery has not been reported previously.